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Article: Mutation of conserved aspartates affect maturation of presenilin 1 and presenilin 2 complexes

TitleMutation of conserved aspartates affect maturation of presenilin 1 and presenilin 2 complexes
Authors
Keywordsγ-secretase
Alzheimer disease
Amyloid β-peptide
Presenilin complexes
Issue Date2000
PublisherBlackwell Munksgaard
Citation
Acta Neurologica Scandinavica, Supplement, 2000, v. 102 n. 176, p. 6-11 How to Cite?
Abstract
Presenilin (PS1 and PS2) holoproteins are transiently incorporated into low molecular weight (MW) complexes. During subsequent incorporation into a higher MW complex, they undergo endoproteolysis to generate stable N- and C-terminal fragments (NTF/CTF). Mutation of either of two conserved aspartate residues in transmembrane domains inhibits both presenilin-endoproteolysis and the proteolytic processing of APP and Notch. We show that aspartate-mutant holoprotein presenilins are not incorporated into the high molecular weight, NTF/CTF-containing complexes. Aspartate-mutant presenilin holo-proteins also preclude entry of endogenous wild-type PS1/PS2 into the high molecular weight complexes, but do not affect the incorporation of wild-type holoproteins into lower molecular weight holoprotein complexes. These data suggest that the loss-of-function aspartate-mutants cause altered PS complex maturation, and argue that the functional presenilin moieties are contained in the high molecular weight presenilin NTF/CTF-containing complexes.
Persistent Identifierhttp://hdl.handle.net/10722/134757
ISSN
ISI Accession Number ID
References

 

Author Affiliations
  1. Adolf-Butenandt-Institut
  2. Toronto Western Hospital University of Toronto
  3. University of Toronto
DC FieldValueLanguage
dc.contributor.authorYu, Gen_HK
dc.contributor.authorChen, Fen_HK
dc.contributor.authorNishimura, Men_HK
dc.contributor.authorSteiner, Hen_HK
dc.contributor.authorTandon, Aen_HK
dc.contributor.authorKawarai, Ten_HK
dc.contributor.authorArawaka, Sen_HK
dc.contributor.authorSupala, Aen_HK
dc.contributor.authorSong, YQen_HK
dc.contributor.authorRogaeva, Een_HK
dc.contributor.authorHolmes, Een_HK
dc.contributor.authorZhang, DMen_HK
dc.contributor.authorMilman, Pen_HK
dc.contributor.authorFraser, Pen_HK
dc.contributor.authorHaass, Cen_HK
dc.contributor.authorSt GeorgeHyslop, Pen_HK
dc.date.accessioned2011-07-14T07:02:50Z-
dc.date.available2011-07-14T07:02:50Z-
dc.date.issued2000en_HK
dc.identifier.citationActa Neurologica Scandinavica, Supplement, 2000, v. 102 n. 176, p. 6-11en_HK
dc.identifier.issn0065-1427en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134757-
dc.description.abstractPresenilin (PS1 and PS2) holoproteins are transiently incorporated into low molecular weight (MW) complexes. During subsequent incorporation into a higher MW complex, they undergo endoproteolysis to generate stable N- and C-terminal fragments (NTF/CTF). Mutation of either of two conserved aspartate residues in transmembrane domains inhibits both presenilin-endoproteolysis and the proteolytic processing of APP and Notch. We show that aspartate-mutant holoprotein presenilins are not incorporated into the high molecular weight, NTF/CTF-containing complexes. Aspartate-mutant presenilin holo-proteins also preclude entry of endogenous wild-type PS1/PS2 into the high molecular weight complexes, but do not affect the incorporation of wild-type holoproteins into lower molecular weight holoprotein complexes. These data suggest that the loss-of-function aspartate-mutants cause altered PS complex maturation, and argue that the functional presenilin moieties are contained in the high molecular weight presenilin NTF/CTF-containing complexes.en_HK
dc.publisherBlackwell Munksgaarden_US
dc.relation.ispartofActa Neurologica Scandinavica, Supplementen_HK
dc.subjectγ-secretaseen_HK
dc.subjectAlzheimer diseaseen_HK
dc.subjectAmyloid β-peptideen_HK
dc.subjectPresenilin complexesen_HK
dc.subject.meshAlzheimer Disease/*physiopathologyen_US
dc.subject.meshAmyloid Precursor Protein Secretasesen_US
dc.subject.meshAmyloid beta-Peptides/metabolismen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAspartic Acid/analogs & derivatives/genetics/*metabolismen_US
dc.subject.meshAspartic Acid Endopeptidasesen_US
dc.subject.meshCell Culture Techniquesen_US
dc.subject.meshCell Membraneen_US
dc.subject.meshDNA, Complementary/geneticsen_US
dc.subject.meshEndopeptidases/metabolismen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHumansen_US
dc.subject.meshMembrane Proteins/*genetics/metabolismen_US
dc.subject.meshMiceen_US
dc.subject.mesh*Point Mutationen_US
dc.subject.meshPresenilin-1en_US
dc.subject.meshPresenilin-2en_US
dc.subject.meshProtein Conformationen_US
dc.titleMutation of conserved aspartates affect maturation of presenilin 1 and presenilin 2 complexesen_HK
dc.typeArticleen_HK
dc.identifier.emailSong, YQ:songy@hkucc.hku.hken_HK
dc.identifier.authoritySong, YQ=rp00488en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1034/j.1600-0404.2000.00301.x-
dc.identifier.pmid11261807en_HK
dc.identifier.scopuseid_2-s2.0-0034571441en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034571441&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume102en_HK
dc.identifier.issue176en_HK
dc.identifier.spage6en_HK
dc.identifier.epage11en_HK
dc.identifier.isiWOS:000167065200002-
dc.publisher.placeDenmarken_HK
dc.identifier.scopusauthoridYu, G=35370376900en_HK
dc.identifier.scopusauthoridChen, F=7404907428en_HK
dc.identifier.scopusauthoridNishimura, M=7403650959en_HK
dc.identifier.scopusauthoridSteiner, H=7203037540en_HK
dc.identifier.scopusauthoridTandon, A=7103281816en_HK
dc.identifier.scopusauthoridKawarai, T=7003632751en_HK
dc.identifier.scopusauthoridArawaka, S=6602984633en_HK
dc.identifier.scopusauthoridSupala, A=6602797868en_HK
dc.identifier.scopusauthoridSong, YQ=7404921212en_HK
dc.identifier.scopusauthoridRogaeva, E=35372614800en_HK
dc.identifier.scopusauthoridHolmes, E=7201667388en_HK
dc.identifier.scopusauthoridZhang, DM=23017363200en_HK
dc.identifier.scopusauthoridMilman, P=7004252433en_HK
dc.identifier.scopusauthoridFraser, P=35408135200en_HK
dc.identifier.scopusauthoridHaass, C=7006070304en_HK
dc.identifier.scopusauthoridSt GeorgeHyslop, P=7005637468en_HK

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